Influence of additives on swelling and mucoadhesion properties of glyceryl monooleate liquid crystals

Abstract Liquid crystalline systems of glyceryl monooleate/water are used as drug delivery systems due to their complex structure that controls drug diffusion. Mucoadhesive properties of glyceryl monooleate suggest it can be used for buccal delivery. Using additives is a strategy to modify physical and chemical properties of liquid crystalline systems and optimize their performance as a drug delivery system. However, the presence of additives can significantly alter properties such as phase behavior, swelling and mucoadhesion. Our aim is to investigate the influence of additives on swelling and mucoadhesion of glyceryl monooleate-based liquid crystals, intending them to be used as buccal drug delivery systems. The systems were characterized regarding their mesophases, swelling rate, and mucoadhesion. All the systems studied were able to absorb water and presented mucoadhesion, which is interesting for the development of buccal drug delivery systems. Additives induced phase transitions and affected the swelling performance, while mucoadhesive properties were poorly affected. Propylene glycol increased water uptake, while oleic acid induced the phase transition to the hexagonal phase and reduced the swelling rate. The association of oleic acid (5%) and propylene glycol (10%) resulted in a cubic phase system with strong mucoadhesive properties that can be a potential drug carrier for buccal delivery.

Organic cocoa extract -loaded surfactant-based systems intended to skin bioadhesion

ABSTRACT This study was to develop, characterize, and evaluate the physical-chemical stability, in vitro antioxidant activity and in vitro safety profile of liquid crystalline systems (LCS) and microemulsions (MEs) with and without organic cocoa (OC) extract. LCS stabilized by surfactant polyoxyethylene 20 cetyl ether, containing water and oleic acid were studied. LCS and MEs were characterized using polarized light microscopy, small angle X-ray scattering, rheology and in vitro bioadhesion, and were evaluated for a period of 30 days by visual aspects, centrifuge test, pH value and relative density. PLM and SAXS assays showed the presence of domains of MEs, cubic and hexagonal mesophasephases, varying the proportions of the components of the formulations; where in the addition of the extract did not change rheological behavior of the formulations. All of the formulations were stable in the period analyzed and presented higher bioadhesive strength. In vitro antioxidant activity suggests that LCS and MEs presented a high capacity to maintain the antioxidant activity of OC extract. The results showed that the incorporation of OC in LCS improved the safety profile, according to cytotoxicity assays of systems may be a promising platform to OC extract for topical application for the potential treatment of skin disorders.

Estudio de la estabilidad de emulsiones con estructuras líquido-cristalinas, y su aplicación farmacéutica mediante el agregado de un principio activo liposoluble: Econazol / Study of emulsions stability with liquid crystals structure and their pharmaceutical application by the addition of a liposoluble principe active: Econazole

La piel es un órgano apropiado para administrar principios activos con el fin de obtener efectos locales o sistémicos. Las formulaciones de uso tópico más comunes son: lociones, emulsiones, suspensiones, cremas, pomadas; las cuales deben reunir determinadas condiciones para ser aplicadas sobre la piel. El objetivo del presente trabajo es seleccionar una emulsión preparada con la técnica de formación de cristales líquidos compuesta de ácido esteárico, vaselina líquida, trietanolamina, propilparabeno, metilparabeno y agua, a la que se le incorpora un ingrediente farmacéutico activo liposoluble: econazol. El econazol, principio activo cuya vía de administración es la tópica y su acción es local, es una sustancia soluble en aceites, que se aloja en la fracción liposoluble de los cristales líquidos y en la fase interna de la emulsión sin que se modifique el perfil reológico ni la estabilidad de los sistemas. Se estudió además del HLB y de sus comportamientos reológicos, la presencia de cristales líquidos con luz polarizada, la existencia de gotas secundarias con luz común y la estabilidad de los sistemas por centrifugación y estrés térmico a temperaturas de 40 ºC. Los valores obtenidos en los estudios realizados, demostraron que la emulsión lograda presenta un perfil reológico y las condiciones de estabilidad adecuadas para ser utilizada como crema medicinal.

The skin is the appropiate organ to administrate active principles in orden to obtain local or systemic effects. Formulations for topical use most common are: lotions, emulsions, suspensions, creams, ointments, which must gather certain conditions to be applied to the skin. In this work, the objective is to select an emulsion prepared by a technique of liquid crystals formation composed by stearic acid, mineral oil, triethanolamine, propylparaben, methylparaben and water. To this formula we incorporated a pharmaceutical active liposoluble ingredient: econazole. Econazole, a principle active with topical administration and local action, is a substance soluble in oils, which stays in the liposoluble fraction of the liquid crystals and in their internal phase of the emulsion without modifying their rheological profile not even the stability of systems. Besides the HLB of the systems and their rheological behaviour we also study the presence of liquid crystals with polarized light, the existence of secondary drops with common light and systems stability by centrifugation, thermal stress and temperatures of 40 °C. The values obtained from the studies made, demonstrated that the emulsion achieved present a rheological profile and stability conditions suitable for medicinal use cream.

Validation of high-performance liquid chromatographic method for analysis of fluconazole in microemulsions and liquid crystals

In recent decades, there has been a significant increase in the incidence of fungal diseases. Certain fungal diseases cause cutaneous lesions and in the usual treatment, generally administred orally, the drug reaches the site of action with difficulty and its concentration is too low. An approach much explored in recent years is the development of nanotechnology-based drug delivery systems, and microemulsions (ME) and liquid crystals (LC) are promising. ME and LC were developed with oleic acid or copaiba oil as the oil phase, propoxyl (5OP) ethoxyl (20 OE) cetyl alcohol as surfactant and water. An analytical method to assess the incorporation of fluconazole (FLU) in the systems under study was validated according to guidelines of the International Conference on Harmonization (ICH) guidelines and the Brazilian Food, Drug and Sanitation Agency (ANVISA). The method was conducted on a C18-RP column (250 × 4.6 mm i.d.), maintained at room temperature. The mobile phase consisted of acetonitrile and water (50:50, v/v), run at a flow rate of 1.0mL/min and using ultraviolet detection at 210nm. The chromatographic separation was obtained with a retention time of 6.3min, and was linear in the range of 20-400 µg/mL (r2=0.9999). The specificity showed no interference of the excipients. The accuracy was 100.76%. The limits of detection and quantitation were 0.057 and 0.172 µg.mL-1, respectively. Moreover, method validation demonstrated satisfactory results for precision and robustness. The proposed method was applied for the analysis of the incorporation of FLU in ME and LC, contributing to improve the quality control and to assure the therapeutic efficacy.

Nas últimas décadas, houve aumento significativo na incidência de doenças fúngicas. Certas doenças fúngicas provocam lesões cutâneas, sendo que no tratamento usual, geralmente administrado por via oral, o medicamento chega ao local de ação com dificuldade, em concentração muito baixa. Uma abordagem muito explorada nos últimos anos é o desenvolvimento de sistemas de administração de fármacos baseados em nanotecnologia, como as microemulsões (ME) e cristais líquidos (LC). ME e LC foram desenvolvidos com o ácido oleico ou óleo de copaíba como fase oleosa, álcool cetílico propoxilado (5 OP) e etoxilado (20 OE) como tensoativo e água. Método analítico para avaliar a incorporação de fluconazol (FLU) nos sistemas em estudo foi validado de acordo com as diretrizes da Conferência Internacional de Harmonização (ICH) e Agência Nacional de Vigilância Sanitária (ANVISA). O método foi desenvolvido empregando coluna C18-RP (250 x 4,6 mm id), mantida à temperatura ambiente. A fase móvel consistiu de acetonitrila e água (50:50, v/v), executado a uma taxa de fluxo de 1,0 mL/min e com detecção ultravioleta a 210 nm. A separação cromatográfica foi obtida com o tempo de retenção de 6,3min, e mostrou-se linear no intervalo de 20-400 µg/mL (r2=0,9999). Pelo estudo de especificidade, observou-se não interferência dos excipientes. A precisão foi 100,76%. Os limites de detecção e de quantificação foram 0,057 e 0,172 µg.mL-1, respectivamente. Além disso, a validação do método demonstrou resultados satisfatórios para a precisão e robustez. O método proposto foi aplicado para a análise da incorporação do FLU em ME e cristais líquidos, contribuindo para aumentar o controle de qualidade e garantir a eficácia terapêutica.

Caracterização do intumescimento de sistemas líquido-cristalinos de fase lamelar de monoleína e água contendo polihexametilenobiguanida / Characterization of swelling of lamellar phases of monoolein and water containing polyhexamethylenebiguanide

A monoleína é um lipídeo polar capaz de absorver água e formar sistemas líquido-cristalinos, os quais são utilizados como sistemas de liberação para administração de vários fármacos. Neste estudo foi avaliado o potencial de sistemas de fase lamelar constituídos por monoleína e água para veicular polihexametilenobiguanida (PHMB). A formação dos sistemas líquido-cristalinos foi caracterizada por microscopia de luz polarizada. Estudos de intumescimento foram realizados gravimetricamente em várias condições avaliando-se os efeitos de parâmetros como pH, força iônica e temperatura do meio de imersão. O processo de intumescimento foi caracterizado através da obtenção dos perfis de intumescimento e análise de sua cinética, além da determinação da capacidade máxima de intumescimento dos sistemas. Os sistemas de fase lamelar foram obtidos em presença de PHMB, os quais absorveram água rapidamente de acordo com cinética de segunda ordem e sofreram transição de fase, formando a fase cúbica. O intumescimento dos sistemas não foi influenciado pela presença do fármaco nos vários meios de imersão estudados, exceto pela imersão em meio ácido, no qual a presença do PHMB aumentou a captação de água. O intumescimento dos sistemas contendo PHMB não foi afetado pela força iônica do meio de imersão, porém foi diminuído com o aumento da temperatura. Desta maneira, sistemas líquido-cristalinos de monoleína e água foram obtidos e o processo de intumescimento foi caracterizado. Os sistemas apresentaram potencial para serem propostos como sistemas de liberação para administração de PHMB e estudos de liberação de fármacos serão realizados futuramente.

Monoolein is a polar lipid that absorbs water and forms liquid crystalline systems that are used as drug delivery systems for different medications. The aim of the present study was to investigate lamellar phases formed by monoolein and water as potential vehicles for the administration of polyhexamethylene biguanide (PHMB). Lamellar phase systems formed by monoolein and water containing PHMB were characterized by polarizing microscopy. Swelling studies were performed gravimetrically under different conditions for the evaluation of the effects of pH, ionic strength and temperature. Analyses of swelling profiles, swelling kinetics and maximum swelling capacity were performed. The lamellar phase systems of monoolein and water obtained in the presence of PHMB absorbed water very quickly following second-order swelling kinetics and formed a cubic phase. The swelling of the systems was not influenced by the presence of the drug in the immersion media studied, except under acidic conditions, in which the drug exhibited increased water uptake. The swelling of systems containing PHMB was not affected by the ionic strength of the immersion media, but was reduced with an increase in temperature. Liquid crystalline systems of monoolein and water were obtained and swelling behavior was investigated. The systems exhibited the potential for use as a drug delivery system for PHMB administration. However, further drug-release studies should be performed.

Atividade antioxidante do extrato seco de cacau orgânico (Theobroma cacao) - estudo de estabilidade e teste de aceitação de cremes acrescidos deste extrato / Antioxidant activity of organic cocoa dried extract (Theobroma cacao), stability study and acceptance testing of cosmetic cream containing this extract

Os frutos de cacau (Theobroma cacao) são conhecidos mundialmente pela sua riqueza em ácidos graxos e compostos fenólicos com poder antioxidante, sendo que em sua constituição é possível relatar mais de 50% em ácidos graxos de cadeia média que o torna matéria-prima passível de ser explorada pela indústria alimentícia, farmacêutica e cosmética. Este trabalho teve como objetivo estudar o poder antioxidante do extrato seco de cacau orgânico, obter formulações cosméticas acrescidas deste extrato, promovendo os estudos de estabilidade, ensaios reológicos e a investigação de cristais-líquidos, bem como realizar o teste de aceitação das mesmas. O extrato vegetal foi avaliado quanto seu poder antioxidante pelo método de sequestro radicalar DPPH. Formulações cosméticas foram obtidas e amostras foram submetidas a ensaios físico-químicos de estabilidade (caracterização organoléptica, teste de centrífuga e determinação dos valores de pH), caracterização reológica, assim como análises em microscopia de luz polarizada. As preparações estáveis também foram avaliadas quanto a sua aceitabilidade por provadores. A partir dos resultados apresentados pôde-se constatar a atividade antioxidante do extrato seco de cacau orgânico e obter preparações cosméticas, constituídas deste ativo a 5%, com comportamento pseudoplástico associado à tixotropia e providas de cristais líquidos lamelares. Verificou-se também que a concentração de cera autoemulsionante interferiu na aceitação do produto cosmético.

The cocoa fruit (Theobroma cacao) is known worldwide for its richness in fatty acids and phenolic compounds, with antioxidant power, and it is known to be composed of more than 50% medium-chain fatty acids, making it a raw material that could be exploited by the food, pharmaceutical and cosmetics industries. the aim of this study was to assess the antioxidant power of organic cocoa dried extract, to develop cosmetic formulations from this extract and to determine their stability and carry out rheological tests, liquid-crystal research and acceptance testing on them. the plant extract was assayed for its antioxidant power by the DPPH radical scavenging method. Cosmetic formulations were produced and samples were subjected to physicochemical stability tests (organoleptic assessment, centrifugal testing and determination of pH), rheological characterization and polarized light microscopy analysis. the stable preparations were also evaluated for their acceptability by consumers. From the results presented, it was possible to characterize the antioxidant activity of dried organic cocoa extract and to prepare cosmetic preparations containing 5% of this active compound. these showed pseudoplastic behavior associated with thixotropy and lamellar liquid crystals were presentat all storage times and temperatures. It was also found that the higher self-emulsifying wax contents interfered with consumer acceptance of the cosmetic product.

Preliminary Researches for the Causes of Maltese-Cross Formed in Biological Liquid Crystals / 昆明医科大学学报

We studied the causes of Maltese-cross formed in biological liquid crystals. We conidered that the Maltese-cross is a kind of interfernce pattern of polarized light which passed through the biological liquid crystal. We had observed different interfernce patterns which were differ- ent shapes of Maltese-cross, under a convergent, perpendicular, polarized light micro- scope because the light-axis direction in biological liquid crystals is at pleasure.